The ultimate goal of this program is to develop a prophylactic or therapeutic agent (derG) for treatment of medically important viral and other infections for which there may not be treatment or the treatment is too toxic. DerG was identified as a new immunostimulatory peptide as a result of work on L.E.A.P.S.TM vaccine technology. The derG peptide is based on sequence from the beta chain of the MHC II molecule and is an altered peptide ligand of the CD4 molecule. Preliminary studies in different laboratories indicate that derG can induce protection against parasitic malarial sporozoite and herpes simplex virus challenge and act as an adjuvant for tumor vaccine therapy. Administration of derG within 3 days (or less) or up to 4 weeks in advance of infectious challenge elicited protection against HSV challenge. The proposed investigation will extend our studies of derG on HSV and determine by using mouse models whether derG protects against viral encephalitis by HSV and an arbovirus, S.A. AR86 sindbis-Iike alphavirus. Our specific aims are to: 1) establish the efficacy of derG against these viruses; 2) develop in vitro assays for derG activity to allow screening of analogues, other drugs and to maximize potential for the following aims; 3) determine the mechanism of action of derG; 4) design and prepare for evaluation derG analogues in vitro and in HSV challenge models and initiate procedures required to pursue FDA approval of derG for human therapy. This project is part of a continued collaboration between an academician and CEL-SCI Inc., a biotechnology-vaccine development company. CEL-SCI is committed to provide support including technological development, quality control, scale up to GMP level development, access to preclinical development, methods for toxicological and pharmacological testing, clinical testing and data management resources. Successful development of derG may provide a broad spectrum, immunoenhancing prophylactic and therapeutic treatment that can be provided in lieu of, or to enhance vaccination prior to travel or assignment to a region of high risk for exposure to infectious or bioterror agents upon short notice. [unreadable] [unreadable]